The mechanism by which the stomach protects itself from autodigestion by the acid contained within its lumen has not been elucidated to date. In this proposal we outline a series of experiments to investigate the role of intrinsic and extrinsic surface-active phospholipids in this protective mechanism. These studies developed from preliminary findings from our laboratory which indicated that: 1) amphoteric phospholipids present in pulmonary surfactant have the capability of increasing the hydrophobic (non-wettable) property of inert and biological surfaces; 2) these same surface-active molecules are present in the gastric juice and mucosal lining; 3) the intact gastric mucosal lining is highly hydrophobic whereas it is rapidly converted to a wettable surface after the stomach is exposed to the barrier breakers, aspirin and bile acid; and 4) acid-induced ulcerogensis and bleeding are markedly reduced if rats are pretreated with an liposomal suspension of extrinsic surface-active phospholipids. It is our contention that these surface-active phospholipids are adsorbed onto the surface of the gastric mucosal surface and in doing so form and non-wettable hydrophobic layer between the acidic luminal contents and the gastric epithelium. In the proposed studies we plan to test this hypothesis by investigating: 1) the relationship between surface hydrophobicity and the integrity of the "Gastric Mucosal Barrier"; 2) the localization of the intrinsic surface-active phospholipids within the gastric mucosa and their cell of origin; 3) the ability of extrinsic phospholipids to protect against contrasting forms of experimentally-induced gastric and duodenal ulcer and 4) the possible mediator role of intrinsic surface-active phospholipids in prostagladin-induced cytoprotection. The latter possibility seems particularly appealing since we have obtained preliminary evidence that prostaglandins acutely stimulate the concentration of surface-active phospholipids within the rodent gastric mucosa.